Animals exposed to different trace metals for prolonged periods of time show metal-specific biological response profile which specifically characterizes exposure to that metal. The objective of these studies is to assess and characterize response profiles based on a thorough understanding of subcellular mechanisms of metal toxicity and specifically to (1) define and correlate ultrastructural and biochemical responses in vivo which characterize exposure to toxic trace elements and (2) develop early, specific, and sensitive biochemical testing procedures that may be used to evaluate human populations exposed to environmentally important trace elements. Specific metals and areas of interest include the biochemical effects of cadmium and lead on cell membrane and mitochondrial structure and function. The relationships between intracellular molecular binding of lead and cadmium and toxic responses of organelle systems are also of intense concern. Cytosolic lead-binding components were found in target tissues for this element and were partially characterized by gel chromatography, electrophoresis and saturation analysis. The binding components appear to be a major initial intracellular compartment for lead entering the cells of target organs. Zinc deficiency enhances cadmium toxicity and increases the amount of non-metallothionein cadmium in rats following cadmium exposure.